皮内注射用卡介苗关键质量指标关联性分析

目的  对皮内注射用卡介苗（卡介苗）关键质量指标进行关联性分析，为生产工艺控制提供一定的依据。方法  用统计软件（Minitab 17和SPSSAU）对211批卡介苗的菌种代次、半成品沉降率、半成品活菌数、成品活菌数、成品效力和成品渗透压摩尔浓度等关键质量指标进行统计分析，探寻各指标间相互影响的规律。结果  第6、9和12代卡介菌生产的卡介苗成品活菌数均值分别为5.07×10⁶、5.49×10⁶和6.02×10⁶ 菌落形成单位（colony-forming unit，CFU）/mg，Pearson相关系数为0.200（P<0.05），成品活菌数随卡介苗生产用菌种代次的升高而略有增加。半成品沉降率处于0.00%~7.99%、8.00%~12.00%和12.00%~20.00%的卡介苗成品活菌数均值分别为5.57×10⁶、5.52×10⁶和5.06×10⁶ CFU/mg，Pearson相关系数为-0.182（P<0.05），成品活菌数随半成品沉降率提高而略有降低。半成品活菌数处于1.00×10⁷~1.99×10⁷、2.00×10⁷~2.99×10⁷和3.00×10⁷~4.00×10⁷ CFU/mg的卡介苗成品活菌数均值分别为4.61×10⁶、5.69×10⁶和6.53×10⁶ CFU/mg，Pearson相关系数为0.537（P<0.05），成品活菌数随半成品活菌数增加而显著增加。成品活菌数处于1.00×10⁶~3.99×10⁶、4.00×10⁶~5.99×10⁶和6.00×10⁶~8.00×10⁶ CFU/mg的卡介苗成品效力均值分别为17.61、16.51和16.55 mm，Pearson相关系数为-0.187（P<0.05），成品效力随成品活菌数增加而先略有降低再趋于平稳。成品活菌数处于1.00×10⁶~3.99×10⁶、4.00×10⁶~5.99×10⁶和6.00×10⁶~8.00×10⁶  CFU/mg的卡介苗成品渗透压摩尔浓度均值分别为363.61、363.21和368.68 mOsmol/kg，Pearson相关系数为0.210（P<0.05），成品渗透压摩尔浓度随着成品活菌数增加而略有升高。结论  在企业标准范围内，成品活菌数受半成品活菌数的影响较大，受菌种代次、半成品沉降率的影响较小。成品活菌数对成品效力和成品渗透压摩尔浓度的影响较小。

Correlation analysis of key quality factors of BCG for intradermal injection

Objective  To analyze the key quality indices of BCG for intradermal injection (BCG), in order to provide some basis for process control. Methods  The key quality indices such as BCG passage, sedimentation rate of final bulk, culturable particle count of final bulk, efficacy of final product and osmolarity of final product of 211 batches of BCG were statistically analyzed, and the correlation between key indices was found using statistical softwares (Minitab 17 and SPSSAU). Results  The average culturable particle counts of final product produced by the 6th, 9th and 12th passage BCGs were 5.07×10⁶, 5.49×10⁶ and 6.02×10⁶ colony-forming unit (CFU)/mg, respectively, the Pearson correlation coefficient was 0.200 (P<0.05). The culturable particle count of final product increased slightly with the increase of BCG passage. The average culturable particle counts of final product for the final bulk sedimentation rates at (0.00-7.99) %, (8.00-11.99) % and (12.00-20.00) % were 5.57×10⁶, 5.52×10⁶ and 5.06×10⁶ CFU/mg, respectively, the Pearson correlation coefficient was -0.182 (P<0.05). The culturable particle count of final product decreased slightly with the increase of sedimentation rate of final bulk. The average culturable particle counts of final product for the final bulk culturable particle counts at (1.00-1.99)×10⁷, (2.00-2.99)×10⁷ and (3.00-4.00)×10⁷ CFU/mg were 4.61×10⁶, 5.69×10⁶ and 6.53×10⁶ CFU/mg, respectively, the Pearson correlation coefficient was 0.537 (P<0.05). The culturable particle count of final product significant increased with the increase of the culturable particle count of final bulk. The average efficacy of final product for the final product culturable particle counts at (1.00-3.99)×10⁶, (4.00-5.99)×10⁶ and (6.00-8.00)×10⁶ CFU/mg were 17.61, 16.51 and 16.55 mm, respectively, the Pearson correlation coefficient was -0.187 (P<0.05). The efficacy of final product decreased at first and then stabilized with the increase of the culturable particle count of final product. The average osmolarity of final product for the final product culturable particle counts at (1.00-3.99)×10⁶, (4.00-5.99)×10⁶ and (6.00-8.00)×10⁶ CFU/mg were 363.61, 363.21 and 368.68 mOsmol/kg, respectively, the Pearson correlation coefficient was 0.210 (P<0.05). The osmolarity of final product increased slightly with the increase of the culturable particle count of final product. Conclusions  At the enterprise standard level, culturable particle count of final product is significantly affected by culturable particle count of final bulk, and slightly affected by BCG passage, sedimentation rate of final bulk. Also, culturable particle count of final product has small effect on the efficacy of final product and the osmolarity of final product.